X-linked adrenoleukodystrophy (X-ALD) is a neurometabolic disease characterized by the accumulation of very-long chain fatty acids (VLCFA) due to the loss of function of the peroxisomal transporter ABDC1. The X-ALD is the most common demyelinizating disease, monogenic inherited with a minimum incidence of 1:17,000 males. Clinically, X-ALD is characterized by a progressive damage to the brain, adrenal gland, peripheral nervous system and eventually death.
X-ALD shows three main phenotypes, an adult adrenomyeloneuropahy (AMN) with axonopathy in spinal cords, a cerebral adrenomyeloneuropathy with brain demyelinization (cAMN) and a childhood variant characterized by severe cerebral demyelinization. Some dietary treatments, for example, Lorenzo's oil, a mixture of glyceryl trioleate and glyceryl trierucate in combination with a diet low in very long chain saturated fatty acids have been used with limited success in the treatment of X-ALD since the levels of VLCFA does not decrease in brain tissues.
The treatment of X-ALD by means of allogenic bone marrow transplantation has been successful when the transplantation is done before getting the disease onset. However, said treatment has several limitations because it can only be done when there is available HLA-matched donor and carries an elevated risk of mortality.
Another therapeutic strategy is based on the use of the histone deacetylase (HDAC) inhibitors 4-phenylbutyrate and valproic acid (ES2303441-B1).
The use of a combination of N-acetylcysteine and alpha lipoic acid has been disclosed as antioxidant therapy for treatment of X-ALD. Said treatment is effective in correcting oxidative damage due to the excess of VLCA. Nevertheless, the exacerbation of oxidative stress in X-ALD, although is associated with the cell damage during the disease progression, is not the cause of the development of the X-ALD itself (ES2377381-B1).
In view of the above, there is a need of new therapies for the treatment of X-ALD directed to molecular targets that trigger said pathology.